Our objectives are (a) to assay tumor induction by X-irradiation, by simulated chemotherapy regimens, and by combined modalities and (b) to learn more about the mechanisms involved. We will utilize the female Sprague-Dawley rat that is genetically predisposed to the development of mammary tumors. At an age of 50-55 days, the rats will be given (a) one of a graded series of X-ray doses (single dose, whole body or half-body) (b) one of a graded series of Malphalan doses simulating a chemotherapy regimen, (c) one of a graded series of Fluorouracil doses simulating a chemotherapy regimen, or (d) combinations of X-ray and drug doses. The induction of subcutaneous mammary tumors and other tumors will be observed for 15 months after treatments. The percentages of rats developing tumors and the average number of tumors per rat as a function of time after exposures to drugs and/or X-rays will be determined for each dose level of each agent. Probit analyses of dose and effect (average number of tumors induced per rat) will be done. The dose/effect curves will be utilized to compare the carcinogenicity of the different "treatments". From an evaluation of the combined modalities, we will learn something about the additivity and the similarity of the tumor induction mechanisms of the three agents.